Acquired immunodeficiency syndrome (AIDS) refers to a condition of HIV (human immunodeficiency virus) infected individuals where immunopotency has gradually decreased and complications easily occur.
Once HIV invaded the body of a host, HIV infects CD4 positive cells, particularly CD4+ T lymphocytes (helper T cells). The protein that is involved in HIV infection of CD4 positive cells is an HIV envelope protein called gp120, which is a glycoprotein with a molecular weight of about 120 kD present in the envelope of HIV and binds to CD4 molecule on cell surfaces as a specific receptor. After infecting CD4+ lymphocytes, HIV invades inside of cells, undergoes uncoating and liberates its nucleic acid (RNA). Then, DNA is synthesized by reverse transcriptase, transcribed and translated. Thus, viral proteins are synthesized. The viral proteins migrate to cell membranes to form virions, which are then released.
Since the antigenic drift of HIV is very frequent, vaccine preparation is difficult and no effective vaccine has been developed yet. Further, since HIV gene is integrated into the chromosomes of infected cells, it is extremely difficult to conduct a drastic treatment of removing the infecting HIV completely.
Currently, drugs such as AZT (azidothymidine) are recognized to be effective in postponing the onset of AIDS and prolonging the lives of patients; and new therapeutics with promising efficacy are being developed one by one. However, no decisive therapeutic has been established yet.
On the other hand, various attempts have been made to obtain antibodies that have the ability to effectively neutralize HIV and are useful for prevention or diagnosis of AIDS. Since gp120 is one of the most important molecules for HIV infection (McDougal et al., Science, 231,382-385 (1986)), it is possible to target gp120 in effective inhibition, prevention and diagnosis of HIV infection. An antibody called “0.5β” has already been prepared which recognizes one epitope present within amino acids 308-331 of the amino acid sequence of gp160, a precursor of the HIV gp120 (Japanese Patent No. 2797099). However, for further enhancing the avidity to antigen, it is necessary to develop high affinity antibodies that can react with the HIV gp120 and effectively neutralize the virus.